RETINOBLASTOMA IN ASSOCIATION WITH THE CHROMOSOME BREAKAGE SYNDROMES FANCONIS-ANEMIA AND BLOOMS-SYNDROME - CLINICAL AND CYTOGENETIC FINDINGS

Two children presenting with sporadic unilateral retinoblastoma and ex hibiting a high degree of chromosome breakage were noted to have unusu al facies, microcephaly and abnormal skin pigmentation. In the first c hild the pattern of both spontaneous and mitomycin-C-induced chromosom e breakage was characteristic of Fanconi's anaemia although the degree of breakage was extreme. She also exhibited a striking increase in X- ray-induced chromosomal damage in Go lymphocytes as measured by dicent ric formation and increase in chromatid-type aberrations. She had a nu mber of typical clinical features, including cafe-au-lait patches and abnormalities involving the kidney; however, she demonstrated neither the hypoplasia of radius and thumb nor the typical aplastic phase of t his disorder. At age 22 months the child became anaemic with trilineag e myelodysplasia, which was rapidly followed by the development of acu te myeloblastic leukaemia. The early onset (at age 4 months) of retino blastoma may have been associated with the underlying genomic instabil ity. The second child exhibited a pattern of chromosome breakage chara cteristic of Bloom's syndrome, in addition to a moderate increase in d amage induced by mytomycin-C. She had the typical stunted growth and m alar hypoplasia of Bloom's syndrome although she did not demonstrate t he frequently described erythematous 'butterfly rash'. Although patien ts with Fanconi's anaemia and Bloom's syndrome are recognised to be at an increased risk of cancel; retinoblastoma has not previously been d escribed in patients with either condition. We suggest that underlying recessive chromosome breakage syndromes may be underdiagnosed in paed iatric cancer patients, with important implications for prognosis and genetic counselling.